Overall objective: To characterize the molecular organization of lipids and proteins in nerve myelin membranes; and to define the molecular interaction that stabilize the membrane arrays. A correlation of biophysical and biochemical technique (including X-ray diffraction, electron microscopy, SDS polyacrylamide gel electrophoresis, immunoblotting, and thin-layer chromatography) applied to different types of specimens (including whole unfixed or fixed tissue, tissue homogenates, tissue fractions, and model systems of lipids and proteins) will be used to address the following specific questions (1) What is the fine-structure and composition of the interlamellar tight junctions of CNS myelin? Computer image analysis will be carried out on electron micrographs. SDS-PAGE/immunoblotting will be used to identify proteins in tissue fractions that are enriched in the junctions. X-ray patterns will be recorded from intact CNS myelin after contrast enhancement of the junctions, and also from tissue fractions enriched in the junctions. (2) What is the arrangement of lipids and proteins in myelin? Correlation between biochemical and X-ray measurements will be made for selected neuron logical mutants of the mouse, certain phylogenetically-older vertebrates, different nerves from within the peripheral nervous system, and isolated myelin preparations. Structural modifications of myelin induced by specific metal cations will be analyzed. The structure and inter-bilayer interaction of multilayers reconstituted from non-denatured proteolipids protein (PLP) plus myelin lipids, and PLP plus myelin basic protein will be analyzed. (3) What is the structural basis of demyelination? The structural and biochemical effects of calcium-ionophore and complement on CNS myelin will be determined. The integrity of interlamellar tight junctions will be examined in white matter from animals having experimental allergic encephalomyelitis and from autopsy material of humans with multiple sclerosis.